Drug Interaction Report

MONITOR: Antifungal medications may interfere with delayed-type hypersensitivity responses to the coccidioidin skin test in patients with a history of pulmonary coccidioidomycosis, potentially resulting in incorrect results. The mechanism of this theoretical interaction is not described in the package labeling, but may involve the ability of antifungal agents to modify cellular functions of the immune system, potentially affecting the patient's delayed-type hypersensitivity reaction to the coccidioidin skin test. Clinical data are limited and conflicting. Receipt of concurrent or previous systemic antifungal therapy did not appear to interfere with or accentuate the induration response to the coccidioidin skin test, according to data obtained from a study in healthy adult subjects who had recently recovered from acute primary pulmonary coccidioidomycosis in Bakersfield, CA and Tucson, AZ. In contrast, a different small study at the Southern Arizona Veterans Affairs Health Care System of subjects with non-meningeal coccidioidomycosis identified receipt of antifungal medication as a factor related to a failure to express delayed-type hypersensitivity to the coccidioidin skin test. However, the authors of this study suggest that factors such as receipt of antifungal medication may be indicators of patients with less intact immunity or more severe coccidioidomycosis and perhaps that is the reason that these patients did not express delayed-type hypersensitivity to the skin test.

MANAGEMENT: Until more data are available, caution may be advisable if use of the coccidioidin skin test is being considered in a patient with a history of pulmonary coccidioidomycosis who is also on systemic antifungal medication(s). Clinicians should be aware of the potential for interference with delayed-type hypersensitivity responses in patients on concomitant antifungal agents.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.